The relationship between CD4⁺ follicular helper T cells and CD8⁺ resident memory T cells: Sisters or distant cousins?

Independent studies over the last decade have characterized the properties of non-circulating CD8+ ‘resident’ memory T cells (T_RM), which offer barrier protective immunity in non-lymphoid tissues and CD4+ follicular helper T cells (T_FH), which mediate B-cell help in lymphoid sites. Despite their very different biological roles in the immune system, intriguing parallels have been noted between the trafficking properties and differentiation cues of these populations, parallels which have only sharpened with recent findings. In this review, we explore the features that underlie these similarities and discuss whether these indicate meaningful homologies in the development of CD8+ T_RM and CD4+ T_FH or reflect resemblances which are only ‘skin-deep’.